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Metformin and Pathologic Complete Responses to Neoadjuvant Chemotherapy in Diabetic Patients With Breast Cancer
Open accessAbstract
Purpose: Population studies have suggested that metformin use in diabetic patients decreases cancer incidence and mortality. Metformin inhibits the growth of cancer cells in vitro and tumors in vivo. However, there is little clinical data to support this. Our purpose was to determine whether metformin use was associated with a change in pathologic complete response (pCR) rates in diabetic patients with breast cancer receiving neoadjuvant chemotherapy. Patients and Methods: We identified 2,529 patients who received neoadjuvant chemotherapy for early-stage breast cancer between 1990 and 2007. Patients were compared by groups: 68 diabetic patients taking metformin, 87 diabetic patients not taking metformin, and 2,374 nondiabetic patients. pCR rates were compared between the three groups using χ 2 tests of independence and compared pair- wise using a binomial test of proportions. Factors predictive of pCR were assessed using a multivariate logistic regression model. Results: The rate of pCR was 24% in the metformin group, 8.0% in the nonmetformin group, and 16% in the nondiabetic group (P = .02). Pairwise comparisons between the metformin and nonmetformin groups (P = .007) and the nonmetformin and nondiabetic groups (P = .04) were significant. Comparison of the pCR rates between the metformin and nondiabetic groups trended toward but did not meet significance (P = .10). Metformin use was independently predictive of pCR (odds ratio, 2.95; P = .04) after adjustment for diabetes, body mass index, age, stage, grade, receptor status, and neoadjuvant taxane use. Conclusion: Diabetic patients with breast cancer receiving metformin and neoadjuvant chemotherapy have a higher pCR rate than do diabetics not receiving metformin. Additional studies to evaluate the potential of metformin as an antitumor agent are warranted.
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“Metformin has also been found to cooperate with neo-adjuvant chemotherapy to result in complete tumor regression in some breast cancer patients (Jiralerspong et al., 2009).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Jiralerspong et al., 2009
In the citing paper
“Type 2 diabetic patients receiving neo-adjuvant chemotherapy for breast cancer as well as metformin were more likely to have pathologic complete response (pCR) than patients not receiving it.”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [156]
In the citing paper
“However, despite the increase in pCR, metformin did not significantly improve the estimated 3-year relapse-free survival rate [156].”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [156]
In the citing paper
“evidence that metformin may also have an adjunctive effect in patients receiving chemotherapy(270)”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [270]
In the citing paper
“There is further evidence that metformin may also have an adjunctive effect in patients receiving chemotherapy(270), and there are now more than 100 ongoing trials”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [270]
In the citing paper
“Metformin treatment was associated with higher pathologic complete response among early-stage breast cancer patients receiving neoadjuvant therapy (95).”
From Diabetes and Cancer (2010) · cites this paper as [95]
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“was associated with a higher chance of pathological complete response (pCR) compared to other antidiabetic therapies [137].”
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“This potential antineoplastic effect of metformin has also been seen in response to neoadjuvant therapy in breast cancer with a higher pathologic complete response rate in metformin [28].”
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“Apart from its hypoglycemic effect, metformin has been found to confer protection against breast cancer (5), polycystic ovary syndrome (6), and neural recovery in patients with brain tumors (7).”
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Metformin regulates ferroptosis in Skin cutaneous melanoma via ATF3/NRF2 axis
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Metadata
- Authors
- Jiralerspong, S., Palla, S. L., Giordano, S. H., Meric-Bernstam, F., Liedtke, C., Barnett, C. M., Hsu, L., Hung, M.-C., Hortobagyi, G. N., & Gonzalez-Angulo, A. M.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- From the Departments of Breast Medical Oncology, Biochemistry and Molecular Biology, Quantitative Sciences, Surgical Oncology, Pharmacy, Molecular and Cellular Oncology, and Systems Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX; and the Department of Gynecology and Obstetrics, University of Muenster, Muenster, Germany.
- Venue
- Journal of Clinical Oncology
- Published
- 2009-07-10
- Volume
- 27
- Issue
- 20
- Pages
- 3297-3302
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC2736070
- OpenAlex
- W2171998898
- Cited by
- 880
- References
- 42
- Citations by year
- 2026: 12 · 2025: 15 · 2024: 18 · 2023: 34 · 2022: 31 · 2021: 51 · 2020: 43 · 2019: 60 · 2018: 34 · 2017: 42 · 2016: 54 · 2015: 53 · 2014: 73 · 2013: 97 · 2012: 76
- FWCI
- 35.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Association for Cancer Research
- Breast Cancer Research Foundation
- Amgen
- American Society of Clinical Oncology
- Deutsche Forschungsgemeinschaft
- National Institutes of Health (5k23ca121994-03)
- National Cancer Institute (1K23CA121994-01), K23-CA121994, 1K23CA121994)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Oncology › Cancer Risks and Factors
- Keywords
- metformin, breast cancer, diabetes mellitus, neoadjuvant chemotherapy, pathological complete response, predictors of treatment response
- MeSH terms
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Diabetes Mellitus, Female, Humans, Hypoglycemic Agents, Metformin, Middle Aged, Remission Induction, Multivariate Analysis, Logistic Models, Survival Analysis, Treatment Outcome, Neoadjuvant Therapy
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